Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera (Po0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression (P ¼ 0.0273 for MMP-2 and P ¼ 0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression (P ¼ 0.0075 for MMP-2 and P ¼ 0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade (P ¼ 0.0511 for MMP-2 and P ¼ 0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.
According to recent statistics, breast cancer remains one of the leading causes of death among women in Western countries. Breast cancer is a complex and heterogeneous disease, presently classified into several subtypes according to their cellular origin. Among breast cancer histotypes, infiltrating ductal carcinoma represents the most common and potentially aggressive form. Despite the current progress achieved in early cancer detection and treatment, including the new generation of molecular therapies, there is still need for identification of multiparametric biomarkers capable of discriminating between cancer subtypes and predicting cancer progression for personalized therapies. One established step in this direction is the proteomic strategy, expected to provide enough information on breast cancer profiling. To this aim, in the present study we analyzed 13 breast cancer tissues and their matched non-tumoral tissues by 2-DE. Collectively, we identified 51 protein spots, corresponding to 34 differentially expressed proteins, which may represent promising candidate biomarkers for molecular-based diagnosis of breast cancer and for pattern discovery. The relevance of these proteins as factors contributing to breast carcinogenesis is discussed.
Thoracentesis plays an important role in cancer patients with symptomatic effusions, although its effect is short-lived and symptoms recur in almost all patients. Early video-thoracoscopic surgical pleurodesis may provide added benefit to a group of patients with advanced cancer presenting with symptomatic malignant pleural effusion. Seventy-six patients with advanced cancer and pleural effusion due to pulmonary-pleural metastases were recruited. In 51 cases (67.1%), at least one thoracentesis was performed before admission for surgery. Preoperative staging consisted of chest radiograph, CT scan, and blood gas analysis. The mean Karnofsky performance status was about 50. Pleurodesis with talc poudrage was completely successful in all patients, with a morbidity rate of 2.6%. There was no post-operative mortality. Three patients (3.9%) underwent further thoracenteses for recurrence of pleural effusion within two months after the procedure. Early use of talc insufflated by video-thoracoscopic surgery is an effective and relatively safe method for treating pleural effusion, and preventing recurrence, in advanced cancer patients.
This work shows correlation between subtypes and the probability of having positive SLN. Patients not expressing vascular invasion, lymphatic invasion and, moreover, a triple-negative tumor subtype may be good candidates for breast conservative surgery without axillary surgical staging.
Second level SLN could be considered only an anomalous lymphatic axillary drainage and it does not linked to particular histological variants of the primitive tumour. In our study, skip metastases were recognized in only 2.6% of cases, therefore, whenever a SLN is not isolated for any reason, the first level sampling represent a viable operative choice.
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